New study hints at biological roots of mental and physical problems in ME/CFS

January 21, 2013

by Simon McGrath

A new study, from Julia Newton’s group in Newcastle, UK, has found evidence that reduced blood flow to the brain is associated with muscle abnormalities in CFS patients.

Earlier work by the same group had found that with many CFS patients, muscles don’t regulate acid levels properly after exercise. Another study, by Ben Natelson, had shown reduced blood flow to the brain of most in a sample of CFS patients. This new study looked at both muscle acidity regulation and blood flow to the brain in the same people with CFS. They found a strong correlation between the two, both at rest and in response to a challenge.

This is tantalising stuff: there is a marked link between factors that potentially underlie physical fatigue (i.e. flawed acid regulation in muscles) and factors potentially affecting mental fatigue (reduced blood flow to the brain, which has been linked to reduced poor cognitive performance). Unfortunately the study is relatively small and they didn’t have the funding to include a control group, so at this stage the findings are tentative.

Links between muscle acidity and brain blood flow at rest

Measurements of brain blood flow and muscle pH were taken for all patients when resting and when challenged. The data from the measurements at rest showed that higher pH (less acid and less ideal) correlated with lower brain blood flow (again, less blood flow is less ideal). The correlation coefficient was 0.67 (on a scale of 0-1.0), which is very high by the standards of CFS research.

Links between muscle acidity and brain blood flow in response to challenge

Many people with ME/CFS find that their problems are provoked when they do something rather than when they are at rest. Using an exercise challenge has proved helpful in revealing abnormalities in CFS patients before, such as the Lights’ gene expression work and the Pacific Labs study of Post-Exertional Malaise.

Muscle challenge

Professor Newton’s group used a similar approach here, with patients repeatedly exercising a calf muscle while muscle pH was measured using Magnetic Resonance Spectroscopy. Compared with expected results (based on previous studies with healthy controls), the muscle pH didn’t recover fully.

Brain blood flow challenge

The ‘challenge’ to brain blood flow was a little different, using something called the ‘Valsalva Manoeuvre’. Here, the patient covers their nose and mouth and tries to exhale hard briefly, before releasing their breath – it’s the same trick you would use to clear blocked ears. This simple procedure triggers a surprisingly complex but predictable series of changes in blood pressure and heart rate as the body brings things back to equilibrium by, for example, contracting blood vessels to raise blood pressure.

Using the Valsalva Manoeuvre as the challenge, researchers measured brain blood flow and found that in CFS patients the final part of the brain blood vessels’ response to the Valsalva Manoeuvre was delayed. What’s more, this delayed response was strongly correlated with poor recovery of muscle pH after exercise (r=0.65, 0-1 scale).

Future promise?

So: both at rest and in response to a challenge, there was a strong correlation between brain blood flow and muscle pH. And in both cases the worse outcome for muscle (higher muscle pH) correlated with the worse outcome for brain blood flow (lower flow/delayed response to challenge).

The previous findings of reduced brain blood flow and muscle dysfunction are interesting, but the new result indicating a strong relationship between the two makes it an area of real promise.

Of course, this is a small study and possibly a similar strong correlation exists in healthy people (albeit at more normal levels of pH/blood flow). What’s needed to advance this area is replication of the findings in studies including matched healthy controls – and Julia Newton is hoping to get funding for just such a study.

Simon McGrath has a biochemistry degree from Oxford University. He later worked for Oxfam, a UK charity. After having ME/CFS for nearly 20 years, he takes a very keen interest in the latest research.

One step closer to reality: ME/CFS is probably related to a mechanical defect in circulating blood to the brain. The body reacts in shock, tries to shut down over over-exertion, HPA axis becomes screwed up. Plus OI/ POT/ NMH. and all those other symptoms result too.

In other words, ME/CFS is probably just a symptom of a genetic condition. That gets triggered by periods of stress or excess inflammatory cytokines. The lactic acid build up she noted is just the body's reaction to a shortage of circulating blood. It is probably a side issue. The strips, and not the zebra.

She didn't consider the other big elephant in the living room: weak connective tissue disorders, most importantly, weak and bulging arteries and veins. The best reason so far why blood is slow to make to the brain. But any progress in the right direction is appreciated. Kudos to Dr. Newton.

One step closer to reality: ME/CFS is probably related to a mechanical defect in circulating blood to the brain. The body reacts in shock, tries to shut down over over-exertion, HPA axis becomes screwed up. Plus OI/ POT/ NMH. and all those other symptoms result too.

In other words, ME/CFS is probably just a symptom of a genetic condition. That gets triggered by periods of stress or excess inflammatory cytokines.

I wish I thought it was that simple. I think things with this illness go further then it just being a genetic condition as that doesnt explain the big ME outbreaks enough when they occur. Genetics I think are only a part of the answer.

She didn't consider the other big elephant in the living room: weak connective tissue disorders, most importantly, weak and bulging arteries and veins. The best reason so far why blood is slow to make to the brain. But any progress in the right direction is appreciated. Kudos to Dr. Newton.

But what about the actual low blood volume in many of us? It takes more then weak, bulging arteries and veins to be causing the body to have actually less blood. Laying a lot or low gravity can affect blood volume if Im remember the studies from astronaunts correctly.. but I think it may be more then just that making our blood volume less in some of us . Ive come to that conclusion as nowdays Im not laying down much at all and are upright "most" of the time (as long as I havent been standing too much).. but I still seem to have actual very low blood volume (indicated by my need to be drinking a lot still and that helps.. and I need to take Florinef for it too).

I agree that connective tissue disorder is probably involved too..but once again. I think that is only a part of the whole thing going on. This illness I think is going to turn out to be a very complex one (A ..genetics + B immune fault?? + C ???some bacteria, virus, fungi, vitamin/mineral deficiency or something = D (ME/CFS) .

I think there's a problem with this sort of study, in that it only looks at 'fatigue', and not 'malaise'. And it seems to almost suggest that a lactic acid build up is a cause of CFS. It's too simplistic, IMO. That's not to say that it couldn't be helpful research, but I'm not convinced that it's the best route to finding answers. I'm not yet up to date with all of Julia Newton's most recent research though, so I've got some reading to do, and I might not yet fully understand the implications or possibilities of this research.

I wish I thought it was that simple. I think things with this illness go further then it just being a genetic condition as that doesnt explain the big ME outbreaks enough when they occur. Genetics I think are only a part of the answer.

I can easily see the outbreaks coexisiting with the low blood flow/ weak tissues theory of ME/CFS. The outbreak or clusters could have originated in a very bad virus that happened to kick off the cascade of nasty immune cytokines. Which caused a higher percentage of vulnerable people to fall into long-term ME/CFS illness. I don't think one theory precludes the other.

Or the outbreaks could have been explained by some exotic, never-seen virus that came and went. The symptoms of our illness are so vague and far flung, as we know, that even doctors have had hard time discerning what is what. Many diseases start with flu-like symptoms; like the flu, for example, or AIDS.

But what about the actual low blood volume in many of us? It takes more then weak, bulging arteries and veins to be causing the body to have actually less blood. Laying a lot or low gravity can affect blood volume if Im remember the studies from astronaunts correctly.. but I think it may be more then just that making our blood volume less in some of us . Ive come to that conclusion as nowdays Im not laying down much at all and are upright "most" of the time (as long as I havent been standing too much).. but I still seem to have actual very low blood volume (indicated by my need to be drinking a lot still and that helps.. and I need to take Florinef for it too).

Yes, it is true, the astronauts did get low blood volume by traveling in low gravity environments. But they were all strong, healthy guys who did not have weak tissue structures. But if our bodies go through a period of stress, and the genetically weak tissues and veins weaken even more, due to cytokines or cortisol, that could be the initiating event for us. The sickness slows the supply to the brain.

When the brain stops receiving the blood, the HPA axis goes into a panic and probably signals for all kinds of other changes, to restore homeostasis. One of the signals could be to slow production of red blood cells. Why produce more cells when it thinks it is not making it to the brain.

BTW Tania, have you ever had your blood cells examined, where they look at the shape of red blood cells? We had several people at the support group meetings back in the 90s who said they had their blood analyzed, and the docs told them their platelets were old, mis-shapen and worn out looking.

At that time, I thought it was just another wishful thinking hooey, sketchy doc making things up to keep the patients coming back. Now i think they might have been on to something. Our bodies are probably not regenerating blood cells at the same rate as a normal person.

Hence, the ones we have get old and worn out looking. An outcome of having perpetually low blood volume. The people who told these stories did seem compelling and believable. I wonder why nobody ever gets that test done anymore? It used to be very popular among CFS patients. I wonder if any of the readers ever had this testing done?

One step closer to reality: ME/CFS is probably related to a mechanical defect in circulating blood to the brain. The body reacts in shock, tries to shut down over over-exertion, HPA axis becomes screwed up. Plus OI/ POT/ NMH. and all those other symptoms result too.

An important thing to keep in mind is that the study is showing correlation, not causation. I think both this article and the study did a good job of keeping that in mind.

For example, if the blood circulation problem was causing other ME symptoms, then those symptoms might disappear when blood circulation to the brain improves, such as while lying down. This doesn't generally help with muscular symptoms, though it does help with cognitive symptoms. Also, a fair number of ME patients get their circulatory issues medically treated to some extent, but this doesn't improve muscular issues either.

I think it's more likely that the correlation between muscular and brain dysfunction comes from an unknown common underlying factor. That is, something could be causing both the deficit in brain circulation and the muscle dysfunction, and potentially other sets of symptoms as well (sleep, GI, etc). Thus when one set of symptoms is successfully treated, there's little effect upon the other symptom sets. This would also explain why some people, even when untreated, could have ME with symptom sets missing, including PEM, if their body is somehow able to compensate in that one area.

Thanks Simon for doing this work. I hadn't been able to review the latest Cardiac paper. Appreciate it. Exciting and hopeful times ahead I think. It might not result in answers and treatment for everyone – or to everyone's satisfaction – but I think it has rightly shined a spotlight on the great prevalence of cardiac and especially autonomic nervous system dysfunction in patients with our diagnosis; and that has to be a good thing.

Thanks Mark and Simon – very interesting …..thinking personally it would explain why at one stage the nurses had great difficulty finding veins to draw blood samples as if they were "collapsed"….vascular problems. One could even speculate that the "patchy high signal changes" on my brain MRI scan had to do with reduced bloodflow.

Thanks Simon for doing this work…. I think it has rightly shined a spotlight on the great prevalence of cardiac and especially autonomic nervous system dysfunction in patients with our diagnosis; and that has to be a good thing.

The paper I've written about here has its own thread: New article by the Newcastle team, the thread you mention cover Julia Newton's work more widely, based on her presentation to the AfME AGM. Both recommended.

I think there's a problem with this sort of study, in that it only looks at 'fatigue', and not 'malaise'. And it seems to almost suggest that a lactic acid build up is a cause of CFS. It's too simplistic, IMO.

Hi Bob

I'm probably guilty of using artistic licence by including 'fatigue'in the title; the study itself just looks at muscle pH and brain blood flow. I don't think they have yet correlated these to fatigue. The incomplete pH recovery in muscles could potentially lead to PEM as well as fatigue itself.Will try to get the blog title changed.

As for lactic acid, it is a little more complicated than that, as they have looked at pH withing muscle cells, not at blood pH, though the plan to do so in detail in future

The Study

We postulate that a compromised skeletal muscle cellular membrane function may lead to the equalisation of the pH between the skeletal muscle intracellular environment and blood, where an increase in intracellular pH (more alkaline) and decrease in blood pH (acidosis) take place, triggering hyperventilation to buffer the pH change in the blood.
…
However, blood acidosis may also affect cellular membrane function, hence the underpinning mechanism of CFS cannot be fully resolved directly in this work, and extensive further work with detailed blood composition analysis is necessary to validate the pathophysiological model implicated here. Nevertheless, our results point to a disease mechanism outside of the CNS, with a peripheral cause.

The evidence for muscle membrane problems in this study is rather limited, but Julia Newton's group have some fascinating work in the pipeline where they have cultured and grown muscle cells from CFS patients (therefore free of e.g. deconditioning and autonomic nervous system problems) – and found defects there too. However, this work has yet to be finalised and published. More about it in Firestormm's transcript of Julia Newton's talk (on page 8 of the pdf).

I had that test done sometime in the early 90s. I can't remember my exact figures but I know it was over 80% of misshapen red blood cells. It was interesting but nobody came up with any ideas for treatment

I'm probably guilty of using artistic licence by including 'fatigue'in the title; the study itself just looks at muscle pH and brain blood flow. I don't think they have yet correlated these to fatigue. The incomplete pH recovery in muscles could potentially lead to PEM as well as fatigue itself.Will try to get the blog title changed.

As for lactic acid, it is a little more complicated than that, as they have looked at pH withing muscle cells, not at blood pH, though the plan to do so in detail in future

The evidence for muscle membrane problems in this study is rather limited, but Julia Newton's group have some fascinating work in the pipeline where they have cultured and grown muscle cells from CFS patients (therefore free of e.g. deconditioning and autonomic nervous system problems) – and found defects there too. However, this work has yet to be finalised and published. More about it in Firestormm's transcript of Julia Newton's talk (on page 8 of the pdf).

Thanks for the info, Simon.
I've got a lot of reading to catch up with, including @Firestormm's transcript.

Very interesting article, Simon.
Could you say something about the diagnostic criteria used to select the participants? I'm wondering how close they would be to CCC/ICC and whether PEM was necessary for inclusion.

Thanks. They used Fukuda, so PEM would have been one of the 8 symptoms, but any 4 of these are needed, none are mandatory apart from fatigue.

Valentijn

An important thing to keep in mind is that the study is showing correlation, not causation. I think both this article and the study did a good job of keeping that in mind.

For example, if the blood circulation problem was causing other ME symptoms, then those symptoms might disappear when blood circulation to the brain improves, such as while lying down. This doesn't generally help with muscular symptoms, though it does help with cognitive symptoms. Also, a fair number of ME patients get their circulatory issues medically treated to some extent, but this doesn't improve muscular issues either.

I think it's more likely that the correlation between muscular and brain dysfunction comes from an unknown common underlying factor. That is, something could be causing both the deficit in brain circulation and the muscle dysfunction, and potentially other sets of symptoms as well (sleep, GI, etc). Thus when one set of symptoms is successfully treated, there's little effect upon the other symptom sets. This would also explain why some people, even when untreated, could have ME with symptom sets missing, including PEM, if their body is somehow able to compensate in that one area.

Yes, it's seems quite likely that both muscle pH and brain blood flow (if confirmed) have a common cause. Though as I metioned in my reply to Bob, the authors speculate that everything else flows from a primary defect in muscle function:

It is possible that CFS is driven by a primary peripheral abnormality that is associated with secondary central sequelae, where a compromised skeletal muscle cellular membrane function underpins the observed abnormalities.

Good point about how one set of symptoms can be tackled independently – i too find lying down makes a big difference to my mental energy, though doesn't have such a big impact on physical fatigue.

taniaaust1

I wish I thought it was that simple….

…I agree that connective tissue disorder is probably involved too..but once again. I think that is only a part of the whole thing going on. This illness I think is going to turn out to be a very complex one (A ..genetics + B immune fault?? + C ???some bacteria, virus, fungi, vitamin/mineral deficiency or something = D (ME/CFS) .

I agree it's likely to be be very comples, perhaps even more than you suggest if there are actually several distinct illnesses withing ME/CFS.

Thanks. They used Fukuda, so PEM would have been one of the 8 symptoms, but any 4 of these are needed, none are mandatory apart from fatigue.

Yes, it's seems quite likely that both muscle pH and brain blood flow (if confirmed) have a common cause. Though as I metioned in my reply to Bob, the authors speculate that everything else flows from a primary defect in muscle function:

Good point about how one set of symptoms can be tackled independently – i too find lying down makes a big difference to my mental energy, though doesn't have such a big impact on physical fatigue.

I agree it's likely to be be very comples, perhaps even more than you suggest if there are actually several distinct illnesses withing ME/CFS.

Yes Simon, PEM is not a required symptom for Fukuda CFS.

It remains unknown even from default subjective claims from Dr Newton's patients of having CFS/ME (because they are labelled with CFS/ME), if anyone even did have ME! (Post exertion worsening of symptoms (relapse) being a classic symptom of ME).

This is the only 'advantage' of DOH's CFS/ME over Fukuda CFS. (DOH CFS/ME requires post exertional worsening of symptoms and Fukuda doesn't).

I had that test done sometime in the early 90s. I can't remember my exact figures but I know it was over 80% of misshapen red blood cells. It was interesting but nobody came up with any ideas for treatment

Hello, I had the same result as you. The 'scientific' term for this finding is altered morphology (shape). It's a sign of hematological dysfunction, probably caused by chronic inflammation.

Here's a paper with a related topic, on red blood cells also (erythrocytes):

It has been hypothesized that a link exists between erythrocyte metabolism (particularly redox metabolism) and erythrocyte shape and that both are related to erythrocyte deformability. The aim of this research is to confirm the results of earlier studies and to investigate a correlation between erythrocyte morphology and erythrocyte oxidative damage in chronic fatigue syndrome (CFS).METHODS:

Reduced glutathione (GSH), malondialdehyde (MDA), methemoglobin (metHb) and 2,3-diphosphoglyceric acid (2,3-DPG) were measured in 31 patients suffering from CFS and 41 healthy control subjects. Scanning electron microscopic studies of the erythrocytes from both groups were also carried out.RESULTS:

There was evidence of oxidative damage in CFS with statistically significant increases in 2,3-DPG (p < 0.05), metHb (p < 0.005) and MDA (p < 0.01). The CFS patients in this study also had significantly more stomatocytes in their blood than the normal subjects (p < 0.005).CONCLUSIONS:

There is a strong likelihood that the increase in erythrocyte antioxidant activity is associated with the presence of stomatocytes. The results of this study provide further evidence for the role of free radicals in the pathogenesis of CFS and a link between erythrocyte metabolism and erythrocyte shape.

Dr Simpson was one of the blood cells shape people. I remember him from a talk he once gave to a group in London. Know he went around the world talking about this test.

Les Simpson's work was largely about RBC flexibility iirc. The membranes were stiff and not able to flex to get through small capillaries easily. This would stuff up microcirculation, but not be obvious in major blood vessels.

I thank you for posting the article and explaining it in "laymen's" terms as much as possible as well as posting the original publications so that those who can understand it can read it.

Whenever I go to the actual publications, I cannot mentally get past the "abstract" much less remember what I just read. (Hmmm… maybe I should be laying down when I read…)

And, thanks to the many comments that dissect the research. Although, I am still waiting for the one article that says "CURE FOR ME/CFS HAS BEEN FOUND!" (not holding my breath), I am still fascinated that there are researchers, Dr's, scientists and others who are working on finding the clues to the puzzle. And I am very pleased to know there are people like Julia Newton still looking for correlations even if they are not causations.

To me, any research is worth noting so ME/CFS patients don't feel like this illness is completely being ignored.

I want to comment on the article: Les Simpson ('Blood Viscosity Factors – the Missing Dimension In Modern Medicine', 'Ramsay's Disease – ME (Myalgic Encephalomyelitis and the Unfortunate Creation of CFS', and contribution to 'A Beginner's Guide to ME/CFS' has done years of research on the way that non-deformable erythrocytes are responsible for the symptoms in muscles, cognition, and endocrine regulation in ME – For some reason his work has up to now been bypassed by the ME research community, although several are familiar with his work. It seems that some fruitful synergy could be created here, and it is very good news that this new work is being done!

Les Simpson's work was largely about RBC flexibility iirc. The membranes were still and not able to flex to get through small capillaries easily. This would stuff up microcirculation, but not be obvious in major blood vessels.

Alex,
I seem recall some of the patients had the following. Don't know if it was in line Simpson's research. My group's patients had other variations in blood shapes too, i can't recall them:

Anisocytosis

Anisocytosis is a medical term meaning that a patient's red blood cells are of unequal size. This is commonly found in anemia and other blood conditions. False diagnostic flagging may be triggered by an elevated WBC count, agglutinated RBCs, RBC fragments, giant platelets or platelet clumps.
The red cell distribution width (RDW) is a measurement of anisocytosis[1] and is calculated as a coefficient of variation of the distribution of RBC volumes divided by the mean corpuscular volume (MCV)

Just realised the heading refers to "mental problems" – just never had – a jump ahead of those around me when slow as I was could point out a water leak to those around me who failed to notice or grasp the implications. Cognitive problems ……slow processing of information only. Intelligence is unimpaired.

It remains unknown even from default subjective claims from Dr Newton's patients of having CFS/ME (because they are labelled with CFS/ME), if anyone even did have ME! (Post exertion worsening of symptoms (relapse) being a classic symptom of ME).

Research 1st

Here's a paper with a related topic, on red blood cells also (erythrocytes):

Erythrocyte oxidative damage in chronic fatigue syndrome. [full text link added by me]
…RESULTS:There was evidence of oxidative damage in CFS with statistically significant increases in 2,3-DPG (p < 0.05), metHb (p < 0.005) and MDA (p < 0.01). The CFS patients in this study also had significantly more stomatocytes in their blood than the normal subjects (p < 0.005).

CONCLUSIONS:There is a strong likelihood that the increase in erythrocyte antioxidant activity is associated with the presence of stomatocytes. The results of this study provide further evidence for the role of free radicals in the pathogenesis of CFS and a link between erythrocyte metabolism and erythrocyte shape.

Hi Research 1st

Interesting paper on CFS vs erythrocyte metabolism/shape. I just checked the full text, and turns outit too uses Fudkuda, ie the same criteria as the Julia Newton study I've written about here – PEM not mandatory:

Patients with chronic fatigue syndrome were recruited through the Chronic Fatigue Syndrome Society, and their diagnosis confirmed by a clinician according to established criteria (16).
[16: Fukuda]

I'm not wild about the Fukuda criteria but they are very widely used and I'm not inclined to dismiss all research out of hand because of using Fukuda. Personally, what I would most like to see is some validated criteria developed i.e. taking a large group of patients diagnosed by a range of criteria and looking at clustering of symptom and biological data. From what I can tell, this is very much what is being planned by the Open Medicine Institute.

The erythrocyte paper concludes:

Further research that has recently commenced in our laboratory will determine whether there is a correlation between erythrocyte form and antioxidant levels

Just realised the heading refers to "mental problems" – sorry never had – not bonkers a jump ahead of those around me like slow as I was could point out a water leak to those around me who failed to grasp – COGNITIVE/PERCEPTUAL problems only.
Ah now who had the mental problems like capacity to ignore the implications – they had I did not. Strange though so incapacited to be brighter………more intelligent.

Ah, probably should have said cognitive! Changed from mental fatigue, as that wasn't strictly accurate but maybe went out of the frying pan into the fire.

Important comments made years ago by Dr. Simpson about abnormally shaped RBCs, hyper-viscous blood in ME patients, and also slowed cerebral blood flow. According to Dr. Newton, there is some kind of impaired blood circulation. The question is why?

Dr. Les Simpson – Rethinking the Pathogenesis of CFIDS

The NZ biologist’s research career began in 1964, studying the New Zealand black mouse as a model for human illnesses such as systemic lupus erythematosus. Shortly after an outbreak of ME (Myalgic encephalomyelitis – the name for CFS most frequently used in New Zealand) in the early 80’s, his attentions began to focus more on the role of blood rheology in ME. He explains, “In the early 1980s, a percipient country doctor recognized an unusual pattern of sickness in his region – which became known as "Tapanui Flu”.

About that time, I became interested in blood rheology [the study of blood flow] using blood filtration and blood viscometry. I was using a filtration technique to assess red cell stiffness. When Dr. Campbell Murdoch was appointed Professor of General Practice, he was soon involved with ME and through his good offices was able to assess ME blood filterability.”

Simpson continues, ”I found that ME blood filtered poorly – implying that they had a problem with blood flow, particularly at capillary level. In a paper published by New Jersey Medicine, I suggested that ME people might have the anatomical feature of smaller than usual capillary diameters. Such a proposal would help to explain the great variety and variation in distribution of the symptoms reported by ME people.”

Other models for the illness have struggled to fit the distinct features of CFIDS, such as exertion intolerance and circulatory dysfunction. Simpson feels impaired blood flow offers a unifying thesis that can explain many of these distinct symptoms. He vividly recalls the unique response to exercise of a patient referred to him. “Two scans were done [SPECT scans] — pre and post exercise. While the pre-exercise scan showed reduced cerebral blood flow, this was much worse in the post-exercise scan. At that time, the effects of physical activity on red cell shape had not been reported. This shows the extent of ignoring blood rheology factors as determinants of blood flow.”

“When you crank up activity levels, symptoms re-surface. Physical activity changes the shape populations of red cells in an additive fashion.” We published a controlled study of the effects of pulling the trigger of a model pistol on red cell shape in ME and controls. The study showed that ME people could not pull the trigger as long as controls before the onset of fatigue – and this was associated with a greater change in the shape populations of red cells. "

While shape changes of red blood cells occur in healthy controls, Simpson says it is the proportion of different types of red blood cells, as well as lower capillary diameter in subsets of patients that may play a large role in undermining proper blood distribution. He does not believe CFIDS is an anemia (a lack or deficiency of red blood cells). “Red cell number is the major determinant of blood viscosity – the main feature of blood rheology. In polycythaemia rubra vera, the high value for red cells is recognized clinically as a cause of the associated increase in blood viscosity.”

“ I never use the word "misshapen" with regards to red cells. The red cells in normal blood fall into 6 different shape classes, and alteration in the cell environment leads to shifts in the proportions of the different cell shapes. Biconcave discocytes (the textbook "normal" red cell) are the most deformable of cells due to the "spare" membrane of the biconcavities. The loss of the concavities when other shapes occur is associated with a reduction in deformability.”
Differing proportions of different shapes of red blood cells can affect blood flow and viscocity. Higher proportions of flat cells ( F-above) may contribute to the high viscocity of blood in CFIDS.

He continues, “Because many capillaries are much smaller than the diameter of the red cell, red cells must change shape to pass through the capillary bed. But shape-changed red cells are stiffer than usual and poorly deformable and they will pass through small capillaries very slowly, or even block the capillary.”

While circulatory dysfunction and post-exertional muscle fatigue are hallmarks of the illness, the symptom set of neurological dysfunction varies widely among sufferers. Simpson believes impaired blood flow can provide a reasonable explanation for the widely varied neurological set of symptoms among individuals with CFIDS/ME.

“As blood flow with normal rates of delivery of oxygen to nerves is essential for normal nerve function, it is very likely that dysfunction of autonomic nerves (as in orthostatic intolerance) could be expected in conditions with changed populations of red cell shapes.

In a 1992 paper published by New Jersey Medicine, I suggested that ME people might have smaller than usual capillary diameters in those parts of the body expressing symptoms. Such a proposal would help to explain the great variety and variation in distribution of the symptoms reported by ME people. ”

At the moment, no education institutions have dedicated programs on haemorheology (study of blood viscosity). He would like to see courses on haemorheology taught at medical schools. “There is a very large medical literature concerning haemorheology – yet the topic is not taught at medical schools – nor is the published information utilized clinically.”

Simpson believes that a body of new ideas on how to more effectively study red blood cells has been published, but this information is yet to be applied properly. Haematologists, he says, “have failed to make the transition from light to electron microscopy. When they use electron microscopy, they do not use immediately fixed red cells – and the textbook concept of a red cell simply shows the effects of treatment prior to fixation.”

Since retiring in 1985, Simpson has sacrificed a large amount of his own time and personal resources to uncover more information about CFIDS/ME. “Since my earliest days with ME, my objective has been to try and improve the well-being of patients.” An attempt by Simpson to establish a clinic to test red blood cells did not survive due to lack of funds, a problem experienced by many researchers interested in CFIDS.

If Simpson’s ideas are correct, agents which improve blood viscosity/flow may relieve symptoms in CFIDS patients. He hopes to someday see placebo-controlled studies conducted “with the primary objective of determining which agent [haemorheological], if any, has the ability to improve patient well-being.” He continues, “Because it is not possible to increase the diameter of a capillary, treatments should be aimed at increasing red cell flexibility. There is published information which reports that TRENTAL (pentoxifylline), fish oil, and oil of evening primrose taken in sufficient amounts (4000mg) improved red cell flexibility.”

I've read about decreased blood flow to the brain before, but I was wondering if I take supplements that increase blood flow to the brain such as Ginkgo Biloba, Vinpocetine, Resveratrol, Grape Seed Extract, Pterostilbene, etc. would that increase the chance of mercury reaching the brain if a person was mercury toxic? I've avoided these supplements since recent troubles with an amalgam, but I'm wondering if I'm being overly cautious.

Hello, I had the same result as you. The 'scientific' term for this finding is altered morphology (shape). It's a sign of hematological dysfunction, probably caused by chronic inflammation.

Here's a paper with a related topic, on red blood cells also (erythrocytes):

Hi Research 1st, thanks for this, very interesting.

I had the 'Live Blood Analysis' a number of years ago. I, too, had many misshapen RBCs. The 'cure' was to eat more protein. Not very helpful, but it was fascinating to see the little buggers on the microscope video monitor. I also have chronic inflammation, but no knows exactly where or why, and they have no interest in finding out.

The mention of oxidative stress make me think of Martin Pall's work on nitric oxide, the "NO/ONOO" stuff, or something like that, and Rich Van K's methylation theories.

Lotus, when these findings came out people with ME and CFS started experimenting with supplements that are said to have these properties in a big way. It was a big topic of discussion. Can't say that anyone reported any worthwhile success with these things at the time. No idea about mercury.

p.s. Dr Simpson suggested fish oils, evening primrose oil and Pentoxifylline at the time. I didn't get a chance to try the Pentoxifylline.

p.p.s. someone has been in contact with Dr Simpson and made him aware of the new research. He is 89 but still replies to emails.

Lotus, when these findings came out people with ME and CFS started experimenting with supplements that are said to have these properties in a big way. It was a big topic of discussion. Can't say that anyone reported any worthwhile success with these things at the time. No idea about mercury.

p.s. Dr Simpson suggested fish oils, evening primrose oil and Pentoxifylline at the time. I didn't get a chance to try the Pentoxifylline.

p.p.s. someone has been in contact with Dr Simpson and made him aware of the new research. He is 89 but still replies to emails.

I found Ginkgo and Vinpocetine to be good for brain fog (although some people have had problems with Vinpocetine) and Resveratrol is good for inflammation. I've also heard good things about Grape Seed Extract and Pterostilbene. They might not solve the problem or even make a huge difference, but I think they're worth trying.

Lotus, the problem is that for many of us we have been trying since the research first came out. For some of use we met Dr Simpson and have been trying ever since then. Been over 20 years since I met him.

It's an area that needs better research and not just into the causes but also treatments. Spending hundreds of pounds each year on supplements that make little difference over a very long period of time is a severe finanacial drain. "tryng" isn't possible to do for decades unless one is has an income.

Not only can my finances afford to do this but my stomach packed up in 2005 and I simply cannot digest all the supplements I was swallowing.

ph abnormality resonates here…for decades I have thought that the reason some meds/foods/supplements 'help', affect me positively, is their clearly off label effect of changing ph; antibiotics do this, hormones, foods…virtually everything has this potential; one doc actually told me outright that he thought it was the saline vehicle and other properties of the cleocin IV's ( NOT cleocin's antibiotic / microbe killing capacity) that made me feel better for a few hours, and I agree, knowing how unpopular this might be…but hey, its a start..

Lotus, the problem is that for many of us we have been trying since the research first came out. For some of use we met Dr Simpson and have been trying ever since then. Been over 20 years since I met him.

It's an area that needs better research and not just into the causes but also treatments. Spending hundreds of pounds each year on supplements that make little difference over a very long period of time is a severe finanacial drain. "tryng" isn't possible to do for decades unless one is has an income.

Not only can my finances afford to do this but my stomach packed up in 2005 and I simply cannot digest all the supplements I was swallowing.

Boy does this ever sound familiar. I would say the most desperate times in post-diagnosis years came when I would spend hour after hour reading about supplements, and walking the isles of health food stores, looking for the one thing that would help me. Both the expense and the disappointment were huge. I took enough supplements over the course of two years to sink a battleship. The only thing that had a "noticeable" effect was vitamin B-12. And even that faded over time. Now looking back, i can say that avoiding certain foods, toxins and eating green vegetables and protein was the only thing that really helps.

Now looking back, i can say that avoiding certain foods, toxins and eating green vegetables and protein was the only thing that really helps.

MishMash.. if you havent done so already.. I suggest to go and have a 2hr glucose test done with the insulin included to get issues there ruled out. Those who have insulin issues feel better on high protein diets (it helps stop the insulin from spiking) along with the avoidance of many other things is needed in those who have this issue. You could have hyperinsulinemia (insulin resistance)… prediabetic state and that can give a lot of symptoms to some of us who have this.

Low blood volume in this illness was found in a study by Dr David Bell in 1998http://www.ncf-net.org/library/Bell-StreetenJCFS1998.htm
This study repeats that. Although any repeat of a physical abnormality in this illness is still welcome.
Blood volume to the brain was also done in the 90's by Dr Jay Goldstein.
The David Bell Study on blood volume was funded by the CFIDS Foundation so that is another good charity to add to the list.

The relation to muscle acidity was something I never knew about. Wouldn't it be great if this study was bigger.

Thanks for doing the interestig reearch; i read most but skimmed some comments
Blood is also a connective tissue ( as is lymph and muscle fascia) so CTD can be implicated in low blood volume in that way too..

the comment re "spouse to spouse tranfer" – transfer has never been demonstrated; an increased incidence among co-habiting people may be due to both having the perhaps latent or unrecognised condition and being together because of that – eg similar habits -eg both like lying in bed and talking/eating as opposed to people who think that is wrong – "you should always be up out of bed in daylight hours" – so they don't hook up in the first place, as they have different and incompatable habits.

I found Ginkgo and Vinpocetine to be good for brain fog (although some people have had problems with Vinpocetine) and Resveratrol is good for inflammation. I've also heard good things about Grape Seed Extract and Pterostilbene. They might not solve the problem or even make a huge difference, but I think they're worth trying.

I have found Ginkgo to be of help for me. For any of you that have tried it before, its either not a right fit for you OR you did not get a good quality extract of it. I've tried many brands before of it, but I always go back to the Vitamin World Ginkgo Biloba brand. Don't know if Vitamin World <not Vitamin Shoppe..they are different> is outside the USA but if you have a chance to get it…I'd recommend that brand. I can "feel" it with this brand moreso than any other brand I've tried. Must be a good quality extract of it.

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